Quorum Regulated Resistance of Vibrio cholerae against Environmental Bacteriophages.

M Mozammel Hoque,Shah M Faruque,John J Mekalanos,Iftekhar Bin Naser,Jun Zhu,S M Nayeemul Bari

doi:10.1038/srep37956

Abstract

Predation by bacteriophages can significantly influence the population structure of bacterial communities. Vibrio cholerae the causative agent of cholera epidemics interacts with numerous phages in the aquatic ecosystem, and in the intestine of cholera patients. Seasonal epidemics of cholera reportedly collapse due to predation of the pathogen by phages. However, it is not clear how sufficient number of the bacteria survive to seed the environment in the subsequent epidemic season. We found that bacterial cell density-dependent gene expression termed “quorum sensing” which is regulated by signal molecules called autoinducers (AIs) can protect V. cholerae against predatory phages. V. cholerae mutant strains carrying inactivated AI synthase genes were significantly more susceptible to multiple phages compared to the parent bacteria. Likewise when mixed cultures of phage and bacteria were supplemented with exogenous autoinducers CAI-1 or AI-2 produced by recombinant strains carrying cloned AI synthase genes, increased survival of V. cholerae and a decrease in phage titer was observed. Mutational analyses suggested that the observed effects of autoinducers are mediated in part through the quorum sensing-dependent production of haemaglutinin protease, and partly through downregulation of phage receptors. These results have implication in developing strategies for phage mediated control of cholera.

Highlights

Toxigenic Vibrio cholerae, the causative agent of the epidemic diarrhoeal disease cholera interacts with numerous bacteriophages both in the aquatic environment and inside the human intestine[1,2,3]
Our results suggest that quorum sensing does modulate the sensitivity of V. cholerae to phage infection through several ways that include extracellular phage inactivation by haemagglutinin protease (HAP) as well as modulation of the function or accessibility of phage to the LPS O-antigen receptor
To examine whether autoinducers CAI-1 and AI-2 enhance the resistance of bacteria against lytic phages, we monitored the kinetics of phage and bacterial growth in mixed cultures of a defined phage and a V. cholerae strain C6706lacZ or its isogenic mutants carrying inactivated autoinducer synthase genes

Summary

Introduction

Toxigenic Vibrio cholerae, the causative agent of the epidemic diarrhoeal disease cholera interacts with numerous bacteriophages both in the aquatic environment and inside the human intestine[1,2,3]. Lytic phages that kill V. cholerae have been shown to play a significant role in modulating the course of epidemics presumably through their inherent bactericidal activity[1,2]. In this latter process, bacterial mutants that are able to resist phage predation (for example, those that have lost cell surface receptors required for phage infection) presumably enjoy a survival advantage. The colonization of the human gut by V. cholerae leads to a state of high bacterial cell density in the intestinal lumen and mucosal surface. Our results suggest that quorum sensing does modulate the sensitivity of V. cholerae to phage infection through several ways that include extracellular phage inactivation by haemagglutinin protease (HAP) as well as modulation of the function or accessibility of phage to the LPS O-antigen receptor

Methods

Results

Conclusion